Process for the preparation of thiophene derivatives and thiophene derivatives obtained therethrough

Abstract

An α-(2-thienyl)propionic acid can easily be prepared in a high yield and high selectivity by reacting a 2-(dihaloacetyl)thiophene which is easily obtainable by acetylation and halogenation of a substituted or unsubstutitued thiophene, with a methylmetal compound and then reacting an alkali metal hydroxide with the reaction product. α-(2-Thienyl)propionic acids are useful compounds from which, for example, thioprofenic acid can easily be prepared. Thioprofenic acid is known as an anti-inflammatory agent. As reaction intermediates, 1-(2-thienyl)-1-dihalomethylethanols can be obtained. Which are novel and useful compounds.

We claim: 
     
       1. A process for preparing an α-(2-thienyl)-propionic acid comprising reacting a 2-(dihaloacetyl)-thiophene of the formula ##STR2## wherein R 1  is selected from the group consisting of hydrogen atom and lower alkyl radicals, R 2  is selected from the group consisting of a hydrogen atom, hydrocarbon radicals and halogen atom, and X is a halogen atom, with a methylmetal compound selected from the group consisting of methylmagnesium halide, methyllithium, dimethylzinc and methylzinc halide under essentially anhydrous conditions in the presence of a solvent and then treating the reaction product with water, thereby forming a 1-(2-thienyl)-1-dihalomethylethanol of the formula ##STR3## and reacting said 1-(2-thienyl)-1-dihalomethylethanol with an alkali metal hydroxide to form an α-(2-thienyl)-propionic acid of the formula ##STR4## 
     
     
       2. A process of claim 1, wherein R 1  is a hydrogen atom or a methyl radical, R 2  is a hydrogen atom, and X is a chlorine or bromine atom, and the methylmetal compound is a methylmagnesium halide. 
     
     
       3. A process of claim 1, wherein the methylation is carried out in the presence of a solvent selected from the group consisting of ethers and hydrocarbons at a temperature of from -78° C. to room temperature, and the reaction with an alkali metal hydroxide is carried out in the presence of a non-polar solvent at a temperature of 0°-50° C. 
     
     
       4. A process of claim 2, wherein 2-(dichloroacetyl)thiophene prepared by a reaction of a 2-acetylthiophene represented by the general formula: ##STR5## with chlorine in the presence of an aliphatic carboxylic acid solvent at a temperature of 0°-50° C. is used as a starting material (in the formula, R 1  represents a hydrogen atom or a methyl radical). 
     
     
       5. A 1-(2-thienyl)-1-dihalomethylethanol represented by the general formula: ##STR6## wherein R 1  is selected from the group consisting of hydrogen atom and lower alkyl radicals, R 2  is selected from the group consisting of hydrogen atom, substituted or unsubstituted hydrocarbon radicals and halogen atom and X represents a halogen atom. 
     
     
       6. A product of claim 5, wherein R 1  is a hydrogen atom or a methyl radical, R 2  is a hydrogen atom, and X is a chlorine or bromine atom.